Cold acclimation and exercise training were previously shown to increase peripheral insulin sensitivity in human volunteers with type 2 diabetes. Although cold is a potent activator of brown adipose tissue, the increase in peripheral insulin sensitivity by cold is largely mediated by events occurring in skeletal muscle and at least partly involves GLUT4 translocation, as is also observed for exercise training. To investigate if cold acclimation and exercise training overlap in the molecular adaptive response in skeletal muscle, we performed transcriptomics analysis on vastus lateralis muscle collected from human subjects before and after 10 days of cold acclimation, as well as before and after a 12-week exercise training intervention. Cold acclimation altered the expression of 756 genes (422 up, 334 down, P < 0.01), while exercise training altered the expression of 665 genes (444 up, 221 down, P < 0.01). Principal Component Analysis, Venn diagram, similarity analysis and Rank–rank Hypergeometric Overlap all indicated significant overlap between cold acclimation and exercise training in upregulated genes, but not in downregulated genes. Overlapping gene regulation was especially evident for genes and pathways associated with extracellular matrix remodeling. Interestingly, the genes most highly induced by cold acclimation were involved in contraction and in signal transduction between nerve and muscle cells, while no significant changes were observed in genes and pathways related to insulin signaling or glucose metabolism. Overall, our results indicate that cold acclimation and exercise training have overlapping effects on gene expression in human skeletal muscle, but strikingly these overlapping genes are designated to pathways related to tissue remodeling rather than metabolic pathways.

中文翻译：

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人类骨骼肌响应冷适应和运动训练的人体志愿者的比较转录组分析。

先前已证明，冷适应和运动训练可增加患有2型糖尿病的人类志愿者的外周胰岛素敏感性。尽管寒冷是棕色脂肪组织的有效激活剂，但寒冷引起的外周胰岛素敏感性增加主要是由骨骼肌中发生的事件介导的，并且至少部分涉及GLUT4易位，这也可以在运动训练中观察到。为了研究冷适应和运动训练在骨骼肌的分子适应性反应中是否重叠，我们对冷适应10天前后，以及12周运动前后从人类受试者采集的外侧股肌进行了转录组学分析培训干预。冷适应改变了756个基因的表达（422个向上，334个向下，P <0.01），运动训练改变了665个基因的表达（444个向上，221个向下，P <0.01）。主成分分析，维恩图，相似性分析和rank-rank超几何重叠均表明上调基因的冷适应和运动训练之间存在明显的重叠，而下调基因则没有。重叠的基因调节对于与细胞外基质重塑相关的基因和途径尤为明显。有趣的是，冷驯化诱导的最高基因与神经细胞和肌肉细胞之间的收缩和信号转导有关，而与胰岛素信号或葡萄糖代谢有关的基因和途径未见明显变化。总体，